We have developed and validated a novel test for the prenatal diagnosis of mucolipidosis IV. The phenotypic alteration that permitted the development of this test is being used as a marker for the functional cloning of the gene that is mutated in mucolipidosis IV. In addition, we have designed a selection procedure for ML4 cells based on their increased sensitivity to chloroquine over normal control fibroblasts. This procedure will allow us to rapidly isolate complementing genes in ML4 cells transfected with DNA libraries. The increase in chloroquine sensitivity also provides a clue to the nature of the abnormal cell biology in patients with ML4.